Abstract

The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 diet for two years. Blood lipid profiles, morphology, and carotid ultrasound of monkeys were measured. Nine of them were euthanized to confirm atherosclerotic lesions. Common carotid arteries (CCA) and carotid bifurcation (BIF) samples were collected and stained using Verhoef-van Giessen and CD68 immunohistochemistry. The results reveal the presence of severe atherosclerosis plaques in six out of nine animals (66.7%) corresponding to intermediately and hyper-responsive groups. The hyper-responsive group displayed the highest response in the developing intimal area (IA) at the CCA (0.821 mm2), whereas the hyporesponsive group had the smallest IA (0.045 mm2) (p = 0.0001). At the BIF, the hyporesponsive group showed the smallest IA (p = 0.001), but there was no difference between the intermediately and hyper-responsive groups (p = 0.312). The macrophage marker CD68 was also expressed on the cartotid of the intermediately and hyper-responsive groups. These results indicate that severe atherosclerotic lesions with high infiltration of macrophages were formed in the carotid arteries of intermediately and hyper-responsive Indonesian cynomolgus monkeys fed with the local atherogenic diet IPB-1 over two years, thus confirming atherosclerosis in a nonhuman primate model.

Highlights

  • The cynomolgus monkey (Macaca fascicularis) is the non-human primate most used in biomedical research after the rhesus monkey (Macaca mulatta)

  • None of the Common carotid arteries (CCA) and BIF sections showed an atherosclerosis lesion grade of VI. These results indicate that the atherosclerosis grade induced by IPB-1 atherogenic diet in the Indonesian cynomolgus monkey is more severe on the BIF compared to the CCA

  • We can conclude that feeding with a local ingredient atherogenic diet for two years can induce atherosclerotic lesions on the carotid arteries of Indonesian cynomolgus monkeys

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Summary

Introduction

The cynomolgus monkey (Macaca fascicularis) is the non-human primate most used in biomedical research after the rhesus monkey (Macaca mulatta). Indonesian cynomolgus monkeys are exported primarily to the United States [1] for biomedical research pertaining to infectious diseases as well as degenerative diseases [2]. The Indonesian cynomolgus monkey (M. fascicularis fascicularis) has a unique genetic profile, which makes it suitable for biomedical research [3]. Cynomolgus is used in biomedical research, with many advantages including anatomical and physiological aspects that are similar to humans, such as in cardiovascular disease [4]. The International Union for Conservation of Nature (IUCN) has reported that the cynomolgus population has significantly decreased, making its status vulnerable [6], which raises awareness regarding the use of cynomolgus monkeys in research

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